Summary of Work: Outer hair cells (OHCs) of the organ of Corti have a membrane-based mechanism for electro-mechanical force generation that operates at auditory frequencies and is believed to play a crucial role in cochlear amplification. This novel mechanism of electromotility produces fast elongation and shortening of the outer hair cell (OHC) driven by changes in membrane potential. It is also presumed that as a by-product of the active vibrations of the inner ear structures an outgoing sound known as the otoacoustic emissions (OAE) is produced. We used a motion analysis system to test whether the putative membrane motor elements in the OHC exhibit short-term conditioning analogous to facilitation or depression for synaptic transmission or inactivation of voltage-gated ion channels. We measured the amplitude of the OHC contraction in response to depolarizations that followed conditioning pulses of different intensities, duration and time interval (TI). OHC motility response showed a limited dependence on a conditioning stimulus, indicating that OHCs are reliable transducers of electrical stimulation. This essential feature of OHCs is needed to operate at auditory frequencies. In another set of experiments we used specific sulfyhydril regents that inhibit outer hair cell electromotility in vitro to test whether they could also inhibit the in vivo OAE. Application of these substances on the round window membrane in anesthetized guinea pigs produced a dose-dependent inhibition of cubic distortion product OAE. This inhibition which developed progressively from high to low frequencies is likely reflecting the diffusion time of the drug from the round window at the base (high frequency region) of the cochlea to the apex (low frequency region). Inhibition was observed for all tested high-intensity stimuli (65-80 dB SPL). These results are consistent with the hypothesis that OHC electromotility is the force generation mechanism for the OAEs.